The goals of this research are the discovery of new intramolecular cycloadditions, the examination of the scope and limitations of these reactions, the development of ways to predict the rates, periselectivities, regioselectivities and stereoselectivities of intramolecular cycloaddition reactions and related reactions in general, and the establishment of the practical synthetic utility of these reactions for the preparation of useful medicinal compounds through the synthesis of several natural products. In the previous grant, intramolecular (6+4), (6+2), (8+2), and (8+6) cycloadditions were discovered, and systematic studies of these reactions were begun. This proposal requests support for further developments of these reactions, and expansion of the scope of our inquiry into the realm of understanding of the rates and selectivities of intramolecular reactions in general. New reactions to be investigated include intramolecular (6+2) cycloadditions involving fulvenes to form non-linearly fused tricyclopentanoids, intramolecular (6+4) cycloadditions with 1, 3- dipoles as the 4 pi electron component, and ene reactions involving 10 electrons instead of the usual 6 electrons. We will investigate the scope and limitations of such intramolecular reactions using side-chains of different lengths and substitution patterns for Diels-Alder, (6+4), (8+2), and (6+2) reactions as well as 1, 3-dipolar, ene and "big ene", reactions. General reactivity and stereochemical rules will be devised, and a force-field will be created for the quantitative prediction of intramolecular cycloaddition rates and products. The results should be of value for the synthesis of natural products and analogs of use in medicinal chemistry.